Lack of effect of glutathione depletion by L-buthionine-S,R-sulfoximine on gentamicin nephrotoxicity in rats.
The mechanism of gentamicin-induced renal proximal tubular cell injury is not known, but generation of reactive oxygen species with subsequent lipid peroxidation has been proposed. In this study, male adult rats were given gentamicin and L-buthionine-S,R-sulfoximine (BSO), a selective glutathione (GSH)-depleting agent, to determine the effects of GSH depletion on acute gentamicin-induced nephrotoxicity. Urinary N-acetyl-beta-glucosaminidase (NAG) excretion increased equally in the groups given gentamicin alone compared to the groups given gentamicin and BSO. BSO treatment alone did not increase NAG excretion. GSH depletion by BSO did not enhance either gentamicin-induced azotemia or the degree of cell necrosis seen by light microscopy. In conclusion, BSO-induced GSH deficiency does not enhance acute gentamicin nephrotoxicity, suggesting that reactive oxygen species are not the major initiating cause of gentamicin-induced acute kidney injury.
Wu
D F
DF
Department of Pharmacology, Cornell University Medical College, New York, N.Y.
Griffith
O W
OW
Reidenberg
M M
MM
D000118:Acetylglucosaminidase / Q000378:metabolism / Q000652:urine; D058186:Acute Kidney Injury / Q000139:chemically induced; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005839:Gentamicins / Q000633:toxicity*; D005978:Glutathione / Q000493:pharmacokinetics*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced; D007687:Kidney Tubules, Proximal / Q000187:drug effects; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000963:Antimetabolites; D005839:Gentamicins; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D003404:Creatinine; D000118:Acetylglucosaminidase; D005978:Glutathione; D010100:Oxygen